The enhancement of cellular internalization and subsequent achievement of a nuclear targeting of nanocarriers play an important role in maximizing the therapeutic potency and minimizing the side effects of encapsulated drugs. Herein, a multifunctional micellar nanoplatform simultaneously with high cell penetration and nuclear targeting through pH‐triggered surface charge reversal is presented. The miscellar system is constructed from poly(ethylene glycol)‐poly(ε‐caprolactone) with 2,3‐dimethylmaleic anhydride‐Tat decoration (PECL/DA‐Tat). DA groups are used to mask the positive charge of Tat to prolong blood circulation of the nanocarriers. In the mildly acidic environment of tumor tissue, the system exhibits ultrasensitive negative to positive charge reversal, facilitating the cell internalization and subsequent nuclear targeting. The chemotherapeutic 10‐hydroxycamptothecin conjugated to methoxy polyethylene glycol, which is loaded in this micelle, obviously enhances cytotoxicity against tumor cells. The in vivo therapy in mice bearing 4T1 breast tumor reveals that the system has a significant enhancement of both the endocytosis and nuclear enrichment, showing a highly effective antitumor efficacy and inhibition to lung metastasis.

中文翻译：

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具有pH触发的细胞穿透和核靶向的多功能胶束纳米平台，可有效治疗癌症并抑制肺转移。

细胞内在化的增强和纳米载体的核靶向的后续实现在最大化治疗效力和最小化封装药物的副作用方面起着重要作用。本文介绍了一种多功能胶束纳米平台，同时具有高细胞渗透性和通过pH触发的表面电荷逆转进行核靶向。杂项系统由具有2,3-二甲基马来酸酐-Tat装饰（PECL / DA-Tat）的聚（乙二醇）-聚（ε-己内酯）构成。DA基团用于掩盖Tat的正电荷，以延长纳米载体的血液循环。在肿瘤组织的弱酸性环境中，该系统表现出对正电荷逆转的超灵敏负电荷，有助于细胞内在化和随后的核靶向。负载在该胶束中的与甲氧基聚乙二醇偶联的10-羟基喜树碱化疗剂明显增强了对肿瘤细胞的细胞毒性。对患有4T1乳腺肿瘤的小鼠进行的体内治疗表明，该系统具有显着增强的内吞作用和核富集作用，显示出非常有效的抗肿瘤功效和对肺转移的抑制作用。